Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Macrophage proteins: structure, function and e-science. The human genome was published five years ago, yet the functions of only a small fraction of the tens of thousands of encoded proteins are known. The development of smarter and faster methods for elucidating the structure and function of uncharacterised proteins is vital to a knowledge-based economy and a healthy society. The long-term benefits to the community will include fundamental new knowledge, generation of new pharmaceuticals and th ....Macrophage proteins: structure, function and e-science. The human genome was published five years ago, yet the functions of only a small fraction of the tens of thousands of encoded proteins are known. The development of smarter and faster methods for elucidating the structure and function of uncharacterised proteins is vital to a knowledge-based economy and a healthy society. The long-term benefits to the community will include fundamental new knowledge, generation of new pharmaceuticals and the development of new eScience approaches to streamline costs and efforts of research and to make science more accessible to the public.Read moreRead less
Development of novel fluorescent proteins from marine organisms for in vivo fluorescence imaging technologies and cancer research. The Australian Great Barrier Reef (GBR) is a national treasure and the development of fluorescent proteins (FPs) from reef organisms for in vivo imaging and biotechnology will enhance the appreciation of this resource. Nowadays, imaging of biochemical processes in living cells is essential for knowing the roles of various genes and proteins in health and diseases. Th ....Development of novel fluorescent proteins from marine organisms for in vivo fluorescence imaging technologies and cancer research. The Australian Great Barrier Reef (GBR) is a national treasure and the development of fluorescent proteins (FPs) from reef organisms for in vivo imaging and biotechnology will enhance the appreciation of this resource. Nowadays, imaging of biochemical processes in living cells is essential for knowing the roles of various genes and proteins in health and diseases. The global market for fluorescence-based products is estimated in billions of dollars p.a. The discovery of natural FPs from GBR with superior molecular, biophysical and optical characteristics to those of commercially available FPs offers a unique opportunity to develop advanced tools to study cellular processes and develop diagnostic assays for diseases such as cancer.Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be ch ....Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be characterised in-field at the site(s) of infection outbreaks. This rapid response is vital, particularly in the event of a pandemic or a deliberate release of the virus in a bioterrorist attack.Read moreRead less
Nanotherapeutics: nanoparticles with high specificity for the delivery and controlled release of drugs. This technology will deliver therapeutic drugs and/or MRI contrast agents to individual diseased cells with very high specificity and selectivity. The cells can be interogated to determine when they are "loaded" and the site of the "loaded" cells precisely determined. Drugs can be released photochemically. The administered dosage can be decreased with no loss of efficacy, and side effects re ....Nanotherapeutics: nanoparticles with high specificity for the delivery and controlled release of drugs. This technology will deliver therapeutic drugs and/or MRI contrast agents to individual diseased cells with very high specificity and selectivity. The cells can be interogated to determine when they are "loaded" and the site of the "loaded" cells precisely determined. Drugs can be released photochemically. The administered dosage can be decreased with no loss of efficacy, and side effects reduced. Read moreRead less